Mammalian target of rapamycin (mTOR) inhibitors and skin cancer risk in nonrenal solid organ transplant recipients: systematic review and meta-analysis.

Abstract

Solid organ transplant recipients have an increased risk of malignancy compared with the general population. Mammalian target of rapamycin (mTOR) inhibitors have been used as immunosuppressants in transplant recipients. There remains a lack of evidence of this treatment in nonrenal solid organ transplantation. We aimed to perform a systematic review and meta-analysis to assess the effects of mTOR inhibitors on secondary nonmelanoma skin cancer(NMSC) malignancies in nonrenal transplant recipients. A systematic review and meta-analysis was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies for the present systematic review and meta-analysis included those in which patient cohorts underwent heart, liver, lung, and pancreas (i.e. nonrenal solid organ) transplantation, with treatment group being those treated with an mTOR inhibitor such as sirolimus or everolimus, and control group being placebo, or alternative non-mTOR inhibitor treatment such as calcineurin inhibitors or as per standard treatment protocol. From the six included studies, we found no significant difference in the odds of either primary or secondary NMSC (OR 0.73, 95% CI 0.41-1.29, P=0.28). Pooled analysis of patients with secondary NMSC demonstrated a trend toward significant benefit with mTOR inhibitor treatment (OR 0.61, 95% CI 0.37-1.02, P=0.06) but no protective effect for primary NMSC (OR 0.53, 95% CI 0.03-9.96, P=0.67). Our results suggest that in nonrenal transplant recipients, mTOR inhibitors may have a protective effect against secondary NMSC but not primary NMSC posttransplantation. Extrapolating the findings of reduced NMSC in renal transplant populations to nonrenal transplant cases should be cautioned.